川芎嗪干预心力衰竭犬心房纤维化及MMP—2与TIMP—2的mRNA表达研究(1)
[摘要] 目的 观察并探讨川芎嗪(TMP)治疗心力衰竭(HF)实验犬心房颤动(AF)与心房纤维化的分子机制。 方法2013年9—12月，我们将健康成年杂种犬21只，随机分为正常对照组、心室快速起搏致HF组和TMP干预组，每组7例。观察TMP干预HF实验犬心房组织纤维化程度与MMP-2及TIMP-2的mRNA表达变化。 结果HF组与对照组相比，AF发生率(2/7 vs 7/7，P<0.001)及持续性AF发生率(0/7 vs 6/7，P<0.001)增加，AF持续时间[(462.1±181.4)s vs (3.24±3.56)s，P<0.001]均明显延长，左右心房纤维化程度亦明显增加[右房(8.36±1.46)% vs(2.88±0.45)%，左房(11.25±1.76)% vs (3.05±0.46)%，P<0.001]且AF持续时间与左心房纤维化程度呈密切正相关(r=0.841，P=0.018)；MMP-2的mRNA表达明显上调[右房(1.16±0.40)vs(0.70±0.22)，P<0.05；左房(3.08±0.76) vs (1.54±0.45)，P<0.001]，而左心房TIMP-2则下调明显[(2.40±0.61)vs(4.47±0.87)，P<0.001]。TMP组相对于HF组，持续性AF诱发率(3/7 vs 6/7，P<0.05)明显降低，纤维化程度下降[右房(5.64±0.99)% vs (8.36±1.46)%，P<0.05；左房(5.46±1.14)% vs (11.25±1.76)%，P<0.001]，而左房MMP-2的mRNA表达明显下调[(1.77±0.50) vs (3.08±0.76)，P<0.01]，左房TIMP-2上调明显[(3.94±0.79) vs (2.40±0.61)，P<0.01]。 结论 TMP通过调节心房组织MMP-2与TIMP-2的mRNA表达改变并促进恢复平衡，可能是其改善HF时心房纤维化并减轻AF发作的分子机制之一。
[关键词] 心房颤动；心力衰竭；川芎嗪；犬
[中图分类号] R4 [文献标识码] A [文章编号] 1674-0742(2015)12(c)-0168-05
Research on Tetramethylpyrazine Phosphate Intervention for Atrial Fibrosis of Heart Failure Dogs and mRNA Expression of MMP-2 and TIMP-2
LIN Ya-zhou1，2， CHEN Lin1，2， LIAN Liang-hua1，2， WU Mei-qiong1，2， CEHN Jian-quan1，2， YANG Zhi-ping1，2
1.Second department of cardiology， Fujian Provincial Hospital， Fuzhou， Fujian Province， 350001 China；2.Provincial Clinical Medical College， Fujian Medical University， Fuzhou， Fujian Province， 350001 China
[Abstract] Objective To observe and discuss the molecular mechanism of TMP in treatment of auricular fibrillation(AF)and atrial fibrosis in the heart failure experimental dogs. Methods 21 healthy adult mongrel dogs from September 2003 to December 2013 were randomly divided into the normal control group， HF group caused by ventricular tachypacing and TMP intervention group with 7 cases in each， the TMP intervention for atrial tissue fibrosis degree and mRNA expression changes of MMP-2 and TIMP-2 were observed. Results Compared with those in the HF group， the incidence of AF(2/7 vs 7/7，P<0.001)and incidence of continuous AF(0/7 vs 6/7，P<0.001)increased， the duration time of AF of both groups was obviously prolonged， [(462.1±181.4)s vs(3.24±3.56)s，P<0.001]， the fibrosis degree of left and right atrium also obviously increased [right atrium (8.36±1.46)% vs(2.88±0.45)%， left atrium (11.25±1.76)% vs(3.05±0.46)%，P<0.001]， and the duration time of AF had a close positive correlation with the fibrosis degree of left atrium，(r=0.841，P=0.018)， and the mRNA expression of MMP-2 in left atrium was obviously down-regulated[(1.77±0.50)vs(3.08±0.76)，P<0.01]， the MMP-2 in left atrium was obviously up-regulated[(3.94±0.79)vs(2.40±0.61)，P<0.01]. Conclusion TMP changes and promotes rebalancing by adjusting the mRNA expression of MMP-2 and TIMP-2 in atrial tissues， and it perhaps is one of molecular mechanisms of atrial fibrosis at the time of improving HF and relieving AF attack. (林亚洲 陈林 连亮华 吴梅琼 陈建泉 杨志平)
[关键词] 心房颤动；心力衰竭；川芎嗪；犬
[中图分类号] R4 [文献标识码] A [文章编号] 1674-0742(2015)12(c)-0168-05
Research on Tetramethylpyrazine Phosphate Intervention for Atrial Fibrosis of Heart Failure Dogs and mRNA Expression of MMP-2 and TIMP-2
LIN Ya-zhou1，2， CHEN Lin1，2， LIAN Liang-hua1，2， WU Mei-qiong1，2， CEHN Jian-quan1，2， YANG Zhi-ping1，2
1.Second department of cardiology， Fujian Provincial Hospital， Fuzhou， Fujian Province， 350001 China；2.Provincial Clinical Medical College， Fujian Medical University， Fuzhou， Fujian Province， 350001 China
[Abstract] Objective To observe and discuss the molecular mechanism of TMP in treatment of auricular fibrillation(AF)and atrial fibrosis in the heart failure experimental dogs. Methods 21 healthy adult mongrel dogs from September 2003 to December 2013 were randomly divided into the normal control group， HF group caused by ventricular tachypacing and TMP intervention group with 7 cases in each， the TMP intervention for atrial tissue fibrosis degree and mRNA expression changes of MMP-2 and TIMP-2 were observed. Results Compared with those in the HF group， the incidence of AF(2/7 vs 7/7，P<0.001)and incidence of continuous AF(0/7 vs 6/7，P<0.001)increased， the duration time of AF of both groups was obviously prolonged， [(462.1±181.4)s vs(3.24±3.56)s，P<0.001]， the fibrosis degree of left and right atrium also obviously increased [right atrium (8.36±1.46)% vs(2.88±0.45)%， left atrium (11.25±1.76)% vs(3.05±0.46)%，P<0.001]， and the duration time of AF had a close positive correlation with the fibrosis degree of left atrium，(r=0.841，P=0.018)， and the mRNA expression of MMP-2 in left atrium was obviously down-regulated[(1.77±0.50)vs(3.08±0.76)，P<0.01]， the MMP-2 in left atrium was obviously up-regulated[(3.94±0.79)vs(2.40±0.61)，P<0.01]. Conclusion TMP changes and promotes rebalancing by adjusting the mRNA expression of MMP-2 and TIMP-2 in atrial tissues， and it perhaps is one of molecular mechanisms of atrial fibrosis at the time of improving HF and relieving AF attack. (林亚洲 陈林 连亮华 吴梅琼 陈建泉 杨志平)